Syntheses and crystal structures of three salts of 1-(4-nitrophenyl)piperazine

The crystal structures and Hirshfeld surface analyses of three salts of 1-(4-nitrophenyl)piperazine with 2-chlorobenzoic acid, 2-bromobenzoic acid and 2-iodobenzoic acid are reported.


Chemical context
Piperazines and substituted piperazines are pharmacophores that can be found in many biologically active compounds across a number of different therapeutic areas (Berkheij, 2005) such as antifungal (Upadhayaya et al., 2004), antibacterial, anti-malarial and anti-psychotic agents (Chaudhary et al., 2006). A review on the current pharmacological and toxicological information for piperazine derivatives was described (Elliott, 2011). 4-(4-Nitrophenyl)piperazin-1-ium chloride monohydrate has been used as an intermediate in the synthesis of anticancer drugs, transcriptase inhibitors and antifungal reagents and is also an important reagent for potassium channel openers, which show considerable biomolecular current-voltage rectification characteristics (Lu, 2007). 4-Nitrophenylpiperazine was the starting material in the synthesis and biological evaluation of piperazine containing hydrazone derivatives (Kaya et al., 2016).

Structural commentary
Structure 1 consists of a 4-nitropiperazinium cation linked to a 2-chlorobenzoate anion by two N-HÁ Á ÁO hydrogen bonds ( Fig. 1, Table 1), which will be discussed in further detail in the Supramolecular features section of the paper. Both the cation and the anion exhibit whole-ion disorder, which was modeled with two equivalent conformations with occupancies of 0.745 (10)/0.255 (10) and 0.563 (13)/0.437 (13) respectively. When discussing the conformations of the anion and cation, only the major components will be used. In the chlorobenzoate anion, the carboxylate group is significantly twisted with respect to the 2-chlorophenyl ring with a dihedral angle of 76.7 (4) , which is likely due to the steric interaction between the ortho-chloro substituent and the carboxylate group. Structures 2 and 3 exhibit similar cation conformations, with equivalent dihedral angles of 65.5 (3) and 67.1 (5) , respectively. Additionally, in all three structures, the 4-nitrophenyl group occupies an equatorial position in its attachment to the piperazinium ring. The molecular structure of 2 with the N-HÁ Á ÁO hydrogen bond shown as a dashed line. Atomic displacement parameters are at the 30% probability level.

Figure 3
The molecular structure of 3 with the N-HÁ Á ÁO hydrogen bond shown as a dashed line. Atomic displacement parameters are at the 30% probability level.
Hydrogen bonds and C-HÁ Á ÁO interactions shown as dashed lines. The half occupancy water molecule is omitted for clarity.
(symmetry code: 1 À x, 1 À y, 1 À z; see Fig. 8 for packing and Fig. 9 for fingerprint plots). Additionally, there are weak C-HÁ Á ÁO interactions between adjacent nitrophenyl rings (symmetry code: 1 À x, 1 À y, Àz) that form an R 2 2 (10) ring. This structure contains a partially occupied water molecule close to a center of inversion for which the hydrogen atoms were not able to be located (see Refinement). This species is likely to be involved in hydrogen bonding with an adjacent oxygen atom in the anion (symmetry code: 1 À x, 1 À y, 1 À z) and with the piperazine ring in the cation, forming an R 3 3 (10) ring. The phenyl rings in adjacent cations forminteractions with a perpendicular distance between centroids of 3.586 (4) Å (symmetry code: Àx, 1 À y, Àz; slippage = 0.379 Å ).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. For all structures, the hydrogen atoms were located in difference maps and relocated to idealized locations (C-H = 0.93-0.97 Å ) and refined as riding with U iso (H) = 1.2U eq (C) while the N-H hydrogen atoms were refined isotropically. For 1, in which both the cation and the anion exhibit whole-ion disorder, two equivalent conformations were modeled with occupancies of 0.745 (10)/ 0.255 (10) and 0.563 (13)/ 0.437 (13) respectively. The water hydrogen atoms were refined isotropically with idealized geometries. SHELXL2018 (Sheldrick, 2015b); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015a); molecular graphics: Olex2 1.5 (Dolomanov et al., 2009); software used to prepare material for publication: Olex2 1.5 (Dolomanov et al., 2009).  Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

4-(4-Nitrophenyl)piperazin-1-ium 2-bromobenzoate hemihydrate (2)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.51 e Å −3 Δρ min = −0.33 e Å −3 Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ. (

4-(4-Nitrophenyl)piperazin-1-ium 2-iodobenzoate hemihydrate (3)
Crystal data Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.